A Novel Glycosylated Ferulic Acid Conjugate: Synthesis, Antioxidative Neuroprotection Activities In Vitro, and Alleviation of Cerebral Ischemia-Reperfusion Injury (CIRI) In Vivo

文献类型： 外文期刊

第一作者： Chen, Jian

作者： Chen, Jian;Yu, Manyou;Zhu, Yongqing;Deng, Junling;Xiang, Zhuoya;Xia, Chen;Yuan, Yongjun;Liu, Qingqing;Tong, Litao;Wang, Fengzhang

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关键词： ferulic acid; glycosylation conjugate; antioxidant; neuroprotection; CIRI

期刊名称：ANTIOXIDANTS （ 影响因子：6.6； 五年影响因子：7.3 ）

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年卷期： 2025 年 14 卷 8 期

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收录情况： SCI

摘要： Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu's protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H2O2-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia-reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP -1.16 +/- 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via center dot OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H2O2-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 mu M) and inhibited excessive cell ROS generation (45.67% at 100 mu M). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS.

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